Examination of Witnesses (Questions 780
- 799)
THURSDAY 20 JANUARY 2005
PROFESSOR SIR
ALASDAIR BRECKENRIDGE
CBE, PROFESSOR KENT
WOODS AND
DR JUNE
RAINE
Q780 John Austin: Can I raise the
issue of Seroxat and your knowledge and involvement. In 1998,
I believe you were on the advisory board of GlaxoSmithKline or
SmithKline Beecham, as it was at the time.
Professor Sir Alasdair Breckenridge:
No, let me just clarify that. From 1992 to 1997 I was a member
of a scientific advisory committee of SmithKline. I resigned from
that in 1997. This had been an extremely valuable exercise for
my development in medicines regulation. We did not discuss specific
products on that board; it was a matter of the larger picture
of industry. I resigned from that in 1997 and this post had been
taken up with the full cognisance of the then MCA. I discussed
this with the MCA and I acted in a totally appropriate manner
with respect to the decisions that I was party to there and in
drugs and medicines regulation.
Q781 John Austin: I was not suggesting
otherwise. My question was whether you were aware or whether the
company made you aware at the time of any testing that they were
doing in relation to Seroxat and the use of Seroxat for children.
Professor Sir Alasdair Breckenridge:
We never discussed any medicines at all. That was never part of
the remit of the scientific advisory board.
Q782 John Austin: It is clear now
that the company were aware of some negative results, particularly
in terms of withdrawal. Were those ever communicated to you either
in your role with SmithKline Beecham or subsequently in your role
with the Committee on Safety of Medicines or the MHRA?
Professor Sir Alasdair Breckenridge:
With respect to me, as I have said already, certainly not and
perhaps Dr Raine might like to answer the question about the communications
to the Agency, if that is your wish.
Q783 John Austin: I also note that
we do not have Dr Ian Hudson with us this morning, although he
was listed as one of the witnesses. Is there a reason why not?
Professor Sir Alasdair Breckenridge:
Yes, Dr Hudson is one of our delegates at the CHMP, the Committee
on Human Medical Products at the EMEA and he is there today. He
is fulfilling a different role for the Agency down there.
Q784 John Austin: Would he have been
able to answer the questions and would he have been aware?
Professor Sir Alasdair Breckenridge:
I cannot answer that on his behalf.
Q785 John Austin: What was his role
at that time?
Professor Sir Alasdair Breckenridge:
I cannot answer that question. I do not know that.
Q786 Chairman: He is a colleague
in the Agency—
Professor Sir Alasdair Breckenridge:
He is the head of licensing in the Agency.
Q787 Chairman: Obviously he played
a very key role in this respect and you have no knowledge of what
that role was? You have not discussed it with him at all?
Professor Sir Alasdair Breckenridge:
No, I have not discussed it with him. He was appointed to the
Agency in 2000 because he was the best candidate for the job to
head up the Licensing Division.
Q788 Chairman: And in advance of
today's session, where no doubt you would have anticipated that
this issue would have been raised, you have not discussed the
possible involvement he may or may not have had?
Professor Sir Alasdair Breckenridge:
I have not discussed that with Dr Hudson at all. I do not know
whether any of my colleagues have, but I have not.
Q789 Dr Taylor: Would you be expected
to be aware of everything that goes on in, for example, the expert
working groups because we are told quite clearly that the expert
working group on SSRIs was given evidence more than 18 months
ago that withdrawal did cause suicidal hostility. Is it beyond
the possibility of a job as large as yours to keep tabs on absolutely
everything that goes on?
Professor Sir Alasdair Breckenridge:
Well, it is, but I have an interest in the field, having served
on the Committee on Safety of Medicines, and I am aware of the
recommendations as they went through, but I was not a member of
the working group and it was not my role to be at them.
Dr Taylor: So we really have not got
anybody here who can answer that specific question?
Q790 John Austin: I think it would
have been useful if Dr Hudson had been here because, as far as
I understand, he was at SmithKline Beecham and his department
was responsible for the collection of adverse reaction information
such as there was with Seroxat.
Professor Sir Alasdair Breckenridge:
Yes, I know that, but I—
Q791 John Austin: So he would have
been a very key witness.
Professor Sir Alasdair Breckenridge:
But I have not discussed that with Dr Hudson.
Q792 John Austin: So you must admit
that it is very unfortunate he is not with us today?
Professor Sir Alasdair Breckenridge:
Well, I apologise for that, but I think there was some confusion
about who was going to attend and I think the Clerk was told that
this was where Dr Hudson was going to be.
Q793 Chairman: It is a little bit
strange then with an issue as sensitive as this that there appears
to have been no discussion within the Agency. Does Professor Woods
want to come in at this point?
Professor Woods: Yes, I would
like to answer that because I do have some information which might
be helpful to you. As Chief Executive, I have discussed with Dr
Hudson his previous role within GSK in relation to the specific
question of Seroxat and he assures me that he has had no direct
personal involvement in those safety issues. However, because
of his role within the company, we agreed, and have since scrupulously
observed, that he should have no role within the Agency in any
decision-making concerned with Seroxat.
Q794 Chairman: And this was not communicated
to Sir Alasdair?
Professor Woods: I would regard
it as an executive matter. I frequently do discuss issues with
Sir Alasdair, but it is something I would consider, as Chief Executive,
as my responsibility.
Q795 John Austin: Presumably, Sir
Alasdair, you were aware that the CSM had an expert working group
which we now know reported in December looking at some of these
issues?
Professor Sir Alasdair Breckenridge:
Yes.
Q796 John Austin: In October you
appeared on a Panorama programme in which you said that
SSRI antidepressants did not cause suicidal behaviour in adults.
Professor Sir Alasdair Breckenridge:
Yes.
Q797 John Austin: That statement
at that time was completely at variance with the findings of the
expert working group which reported two months later.
Professor Sir Alasdair Breckenridge:
No, with all respect, what the expert working group reported were
two things. Firstly, in May 2003, we said that with respect to
children there was an increase in suicidal ideation in children
and no benefits, and that was May 2003. In 2004, the results of
the expert working group said that whilst the SSRIs were clearly
beneficial in adults, there was no evidence of increased suicide
or suicidal thoughts compared to the times before the patients
took the medicines. This was highlighted by the large studies
which had been undertaken, three large studies, using the GPRD
database, comparing SSRIs with the tricyclic antidepressants and
there was no increase in suicidal behaviour due to the SSRIs.
My own belief is that clearly in depression suicide is a huge
problem. When the patient starts to take SSRIs, there is a period
of time before benefit takes place and in that time before benefit
takes place the patient is at great risk of suicide and this is
a time when there must be intense monitoring and great care taken
of the patient.
Q798 John Austin: Could I also ask
you in relation to this that after the report was published the
MHRA informed doctors, following the report, that SSRIs were effective
medicines in the treatment of depression and anxiety conditions.
Now, nobody is disputing that, but do you not think that that
required some qualification both in relation to the expert working
group's report and also into the lack of evidence of the efficacy
of the products in treating mild depression?
Professor Sir Alasdair Breckenridge:
Sorry, maybe I am not picking this up, but you have quoted the
results of the expert working group quite rightly and this is
the line which we have consistently followed. Perhaps there is
something else in your question which I do not understand.
Q799 John Austin: Well, after the
report, my understanding is that your information to doctors merely
stated that these are effective medicines in the treatment of
depression and anxiety and did not have any qualification to that.
Professor Sir Alasdair Breckenridge:
Yes, it did, it had qualifications. What the expert working group
did was to look at three issues about antidepressants: firstly,
the question of withdrawal; secondly, the question of suicidal
ideation; and, thirdly, the question of dose. The problem of withdrawal
has been well known with antidepressants, especially Seroxat,
and I happen to have before me the information sheet, the data
sheet which we published, which the MCA published in 1990 when
Seroxat was first licensed. If I can just read it to you, it says,
"As with many psychoactive medicines, it may be advisable
to discontinue therapy gradually as abrupt discontinuation may
lead to symptoms, such as dizziness, sensory disturbances, sleep
disturbances, agitation or anxiety, nausea, sweating and confusion".
That was in 1990. We returned to that in 1993 in our journal Current
Problems in Pharmacovigilance and we published an article
on this again in 2000, so this is an issue which we have worried
about and kept under review for a long time. The second issue
which came up at the expert working group was suicidal thoughts
to which you have referred already and the third issue was that
of dose. If I return to the data sheet in 1990, the data said
that the recommended dose was 20 milligrams and in some patients
if it was necessary to increase the dose, this should be done
gradually and that is still what the data sheet says today.
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